1-Halo- and 1-lower alkoxy-4-trichloromethylphthalazines

ABSTRACT

1-halo- and 1-lower alkoxy-4-trichloromethylphthalazines are disclosed as fungicides and as novel compositions of matter.

This is a division of application Ser. No. 844,004, filed Oct. 20, 1977,now U.S. Pat. No. 4,139,622.

BACKGROUND OF THE INVENTION

1. Field of the Present Invention

The present invention relates to 1-halo- or 1-loweralkoxy-4-trichloromethylphthalazines and their use as fungicides.

2. Description of the Prior Art

Heterocyclic ring compounds which have both a trichloromethyl and eithera halo or lower alkoxy group attached to the heterocyclic ring have beenknown as effective fungicides. See U.S. Pat. Nos. 3,260,588 and3,260,725, both issued to Hansjuergen A. Schroeder on July 12, 1966.However, applicants believe that until the present invention disclosedherein no one has investigated using phthalazines having thesecombinations of substituents as fungicides.

BRIEF SUMMARY OF THE INVENTION

The present invention is directed toward1-halo-4-trichloromethylphthalazines and 1-loweralkoxy-4-trichloromethylphthalazines as novel compositions of matter.

The present invention also comprises a method for controlling fungi bycontacting them with a fungicidally effective amount of any of thesecompounds or combinations thereof.

DETAILED DESCRIPTION

The above-mentioned 1-halo- or 1-lower alkoxy-4-trichloromethylphthalazine compunds may be prepared commercially from1-halo-4-methylphthalazines by the reactions represented by equation (I)below. The starting compound is chlorinated with UV irradiation underany conventionally known conditions to convert the methyl group to atrichloromethyl group. The resulting 1-halo-4-trichloromethylphthalazinethen can be converted to a 1-lower alkoxy-4-trichloromethylphthalazinecompound by any conventionally known alkoxidation reaction conditionssuch as by employing sodium ethoxide as is illustrated in equation (I).The term "halo" as used in the present specification and claims includeschloro, bromo, and iodo groups; however, it does not include fluorogroups. The preferred halo group is chloro. The term "lower alkoxy" asused herein refers to alkoxy groups having from one to four carbonatoms. The preferred lower alkoxy groups is ethoxy. ##STR1## where X isa halo group.

The specific reaction conditions employed in the above-mentionedphotochlorination and ethoxidation steps are not critical parameters ofthe present invention and any such generally known conditions forcarrying out these types of such reactions may be employed herein. Thus,the present invention is not to be limited in any way to any particularmethod of making the above-mentioned compounds. For example, thephotochlorination step can be carried out by bubbling under UVirradiation a molar excess of chlorine gas through a reactor thatcontains the 1-halo-4-methylphthalazine starting material in a suitablesolvent such as any high boiling chlorinated benzene solvent. Preferredsolvents for the photochlorination step in both of the above reactionsequences include chlorobenzene and ortho-dichlorobenzene. The reactiontemperature of this photochlorination step is preferably from about 100°C. to about 160° C., more preferably from about 110° C. to about 145° C.and most preferably from about 120° C. to about 140° C. because at lowertemperatures the chlorination reaction may be relatively slow. Thereaction pressure is most preferably at atmospheric for economicconsiderations. The reaction is normally allowed to run until no changein the reaction mixture can be seen through analysis. After completionof the reaction, the 1-halo-4-trichloromethylphthalazine product can beeasily recovered from the reaction mixture by any conventional recoverytechnique such as distillation or recrystallization.

The ethoxidation step, as indicated above in equations (I) and (II), maybe carried out in any conventionally known manner. For example, it maybe desirable to simply combine a suitable alkoxidation agent with1-halo-4-trichloromethylphthalazine. Normally, alkali metal alkoxidessuch as sodium ethoxide are the most preferred alkoxidation agents.Sodium ethoxide is especially favored for ethoxidation reactions becauseit is widely commercially available today. However, it may bealternatively desirable to create the alkoxidation agent in situ in thereaction mixture. For example, this can be easily done by addingequivalent weights of sodium and a lower alcohol such as ethanol to thereaction mixture and allowing these two compounds to react to formsodium alkoxide. This just-created sodium ethoxide can then react toform the desired 1-lower alkoxy-4-trichloromethylphthalazine product.Normally, it is preferred to carry out this reaction at or below roomtemperature such as from about 0° C. to about 40° C. under atmosphericpressure. Furthermore, this alkoxidation reaction is usually carried outin a polar organic solvent such as tetrahydrofuran. However, it shouldbe noted that sodium ethoxide is not stable in water. Like thephotochlorination reaction, this second reaction is normally allowed toproceed until no further change in the composition of the reactionmixture was noted. Also, any conventional recovery method may beemployed.

In accordance with the present invention, it has been found that1-halo-4-trichloromethylphthalazine and 1-loweralkoxy-4-trichloromethylphthalazine, either singly or in mixturesthereof, can be utilized as fungicides. Furthermore, it has also beenfound that 1-lower alkoxy-4-trichloromethylphthalazine such as1-ethoxy-4-trichloromethylphthalazine can be utilized as an effectiveinsecticide.

In practicing the process of the present invention, fungi and insectsare contacted with a fungicidally or insecticidally effective amount ofthese above-mentioned compounds. It is to be understood that the terms"fungicidally effective amount" and "insecticidally effective amount" asused in the specification and claims herein is intended to include anyamount that will kill or control said fungi or insects when eitheremployed by itself (i.e., in full concentration) or in sufficientconcentration within a carrier or other substance. Of course, thisamount may be constantly changing because of the possible variations inmany parameters. Some of these may include: the number and type of fungiand insects to be controlled or killed; the type of media to which thepresent compounds can be applied (e.g., plants or crops, insect breedinggrounds); degree of effectiveness required; and type of carrier if any.

This step of contacting may be accomplished by applying these compoundsto the fungi or insects themselves, their habitat, breeding grounds,dietary media such as vegetation, crops and the like, and plant andanimal life, including many which these pests may attack. In the case offungi, it is preferable to apply the chemicals of the present inventionto the dietary media or soil which they infest. In the case of insects,it may be advantageous to apply 1-loweralkoxy-4-trichloromethylphthalazines to the eggs of these insects, tothe insects themselves, or to the insect larvae, the larvae habitat orthe larvae dietary media. At the egg and larvae stages of the insectscycle, the insect is usually relatively stationary and the insecticidecan be applied in a more economical fashion with a greater expectationof good results.

The above-mentioned compounds of the present invention may be formulatedand applied by any conventional methods that include using the chemicalsalone or with a carrier or other substances which may enhance theeffectiveness of the chemical or facilitate handling. Moreover, theactivity of the present compounds may be broadened by the additionthereto of other known biocides.

Specific methods of formulating and applying these active compoundsinclude applying them in the form of dusts, dust or emulsionconcentrates, wettable powders and concentrates, granulates,dispersions, sprays, solutions and the like.

The dusts are usually prepared by simply grinding together from about 1%to 15% by weight of any of these four active compounds with a finelydivided inert diluent such as walnut flour, diatomaceous earth, fullersearth, attaclay, talc or kaolin. Dust concentrates are made in similarfashion excepting that about 16% to 75% by weight of active compound isground usually together with the diluent. In practice, dust concentratesare then generally admixed at the site of use with more inert diluentbefore it is applied to the plant foliage or animals which are to beprotected from fungi or insect attack.

Wettable powders are generally prepared in the same manner as dustconcentrates, but usually about 1% to 10% by weight of a dispersingagent, for example, an alkali metal lignosulfonate and about 1% to 10%of a surfactant, such as a non-ionic surfactant, are incorporated in theformulation. For application to agronomic crops, shrubs, ornamentals andthe like, the wettable powder is usually dispersed in water and appliedas a spray. For treatment of warm-blooded animals, this same spray-typeapplication may be used or the wettable powder may be dispersed in thewater of a dipping trough through which the animals are driven.

Emulsifiable liquids may be prepared by dissolving the active compoundin an organic solvent, such as xylene or acetone, and admixing the thusformed solution with a surfactant or an emulsifier. The emulsifiedliquid is then generally dispersed in water for spray or dipapplication.

It is possible to formulate granulates whereby these active compoundsare dissolved in an organic solvent and the resulting solution is thenapplied to a granulated mineral or the like (e.g., bentonite, SiO₂, orthe like) followed by evaporating off the organic solvent. Granulatescan also be obtained by the compacting of the carrier material with theactive substance and then reducing this compacted material in size.

Furthermore, the applied formulations of the present invention includeother liquid preparations such as dispersions, sprays or solutions. Forthese purposes, one of the above-mentioned active compounds, or morethan one active compound, is normally dissolved in a suitable organicsolvent, solvent mixtures or water. As organic solvents, it is possibleto use any suitable aliphatic and aromatic hydrocarbon or theirderivatives. It is preferred that the solvent be odorless and, moreover,be inert to the active compound.

It should be clearly understood that the fungicide or insecticideformulations, the ingredients which may make up such formulations otherthan the active compounds and the dosages, and means of applying theseformulations may include all known and conventional substances, amountsand means, respectively, that are suitable for obtaining the desiredfungicidal and/or insecticidal result. And, therefore, such processparameters are not critical to the present invention.

Fungicides and insecticides of the present invention may be effectivefor the control of broad classes of fungi and insects and the latter'seggs and larvae. Specific illustrations of fungi wherein fungicidalactivity has been shown include bean powdery mildew, rice leaf spot andbean rust. Specific illustrations of insects wherein insecticidalactivity has been shown include Southern armyworm larvae and Mexicanbean beetle larvae.

The following examples further illustrate the present invention. Allparts and percentages employed therein are by weight unless otherwiseindicated.

EXAMPLE I Preparation of 1-chloro-4-trichloromethylphthalazine

50 grams (0.28 gram-moles) of 1-chloro-4-methylphthalazine was placed in500 milliliters of chlorobenzene in a glass reaction vessel. Gaseouschlorine was bubbled up through the reaction mixture while the reactiontemperature was held at reflux temperature (approximately 130° C.).During this time the reaction mixture was exposed to UV irradiation froma high intensity UV lamp. The chlorination was monitored by Vapor PhaseChromotography (VPC) and was continued until no further change in thecomposition of the reaction mixture was noted. Most of the solvent wasthen removed by vacuum distillation and a solid residue remained whichwas dried. The dried product weighed 49.1 grams and had a melting pointof about 146°-149° C. Elemental and mass spectral analyses confirm theproduct as 1-chloro-4-trichloromethylphthalazine.

EXAMPLE II Preparation of 1-ethoxy-4-trichloromethylphthalazine

14 grams (0.05 gram-moles) of 1-chloro-4-trichloromethylphthalazine wasplaced in 150 ml of ethanol in a glass reaction vessel. A solution of1.2 grams (0.05 mole) of sodium in ethanol was added and the mixturerefluxed at room temperature for two hours. The sodium and ethanolreacted to form sodium ethoxide in situ which in turn reacted with thephthalazine compound. The solids present in the reaction mixture werefirst filtered off leaving a liquid filtrate. This filtrate was thencooled to crystallize a solid product. The filtrate was removed and theproduct dried. The product weighed 6.1 grams of product with a meltingpoint of 171°-172° C. Elemental and mass spectral analyses confirmedthat the product was 1-ethoxy-4-trichloromethylphthalazine.

These active materials formed in Examples 1 and 2 were then tested foractivity as effective foliar fungicides and in the case of the lattercompound, as an effective insecticide.

A uniform aqueous dispersion of each chemical was first prepared. Thisdispersion was made by dissolving each chemical in a solution of acetonecontaining the surfactant TRITON X-155¹ (concentration 1000 parts permillion). Next, this solution is diluted with water 1:9 to obtain astock solution of 10% by volume acetone and 90% by volume water with 100ppm TRITON X-155 and the test chemcial contained therein. This stocksolution was diluted further with water/acetone mix to provide thedesired concentration of the test material, if required.

¹ Manufactured by Rohm and Haas of Philadelphia, PA. and is a poly-etheralcohol.

The aqueous solutions containing each chemical were applied to variousplants according to the methods stated below. These tests were designedto evaluate the ability of each chemical to protect non-infected foliageand eradicate recently established infection against major types offungi such as leaf spot, rust, and mildew that attack above-ground partsof plants.

EXAMPLES III AND IV

Bean plants with incipient infection of bean powdery mildew, (Erysiphepolygoni DC) which have fully expanded leaves and are in 21/2 inch potsare atomized (sprayed) with an aqueous solution of one of the chemicalsof the present invention. The aqueous solution contained 260 parts permillion of each chemical and the atomization operation occurred whilerotating the plants on a turntable. Immediately afterwards, the pottingsoil was drenched with 21 ml of a 520 ppm stock solution (equivalent to25 lb/acre) for each chemical. After seven days, observations are madeon the eradication of established infection present on the primaryleaves at the time of spraying. The leaves are rated on a scale of from0 (no suppression) to 10 (complete eradication or prevention ofinfection). The test results are given in Table 1 below.

EXAMPLE V

Pinto beans, which were in 21/2 inch pots and 9 to 12 days old, weresprayed with an aqueous solution of1-chloro-4-trichloromethylphthalazine. The young plants were sprayedwhile rotating the plants on a turntable and the aqueous solutioncontained 260 parts per million of the chemical. At the same time, 21milliliters of an aqueous solution containing 520 parts per million waspoured on the surface of the potting soil. After the spray deposit haddried, the plants were atomized with a suspension of uredospores [summerspore stages of Bean rust (Uromyces phaseoli)] and placed in a moistchamber at 70° F. for 24 hours. After 7 to 9 days the severity ofpastule formation is rated on a scale of from 0 (no inhibition) to 10(complete inhibition). The test results are given in Table I below.

EXAMPLES VI AND VII

The fully expanded young leaves of a rice, cultivar Starr Bonnet, whichwere about two weeks old and growing in 21/2 inch pots, were sprayedwith an aqueous solution which contained a chemical of the presentinvention. The young plants were sprayed while rotating on a turntablewith the aqueous solution which contained 260 ppm of the chemical.Immediately afterwards, the soil in each pot was drenched with 21milliliters of a 520 ppm suspension (equivalent to 25 lb/acre) of thechemical. After the spray dries, the plants were atomized with aconidial suspension of Rice brown spot (Helminthospoium oryzae B. de H.)and placed in a moist chamber at 75° F. for 24 hours to facilitateinfection. After discrete lesions appear in the unprotected controls(two days later), the infection is rated on a scale of from 0 (noinhibition) to 10 (complete inhibition of infection). The test resultsare given in Table I below.

                                      TABLE I                                     __________________________________________________________________________    FUNGICIDAL ACTIVITY                                                                                   Conc. of Chemical                                                                       Effectiveness Against                       Example                                                                            Chemical           in Solution                                                                             Powdery Mildew                                                                         Bean Rust                                                                           Rice Leaf                    __________________________________________________________________________                                                     Spot                         III  1-chloro-4-trichloromethylphthalazine                                                            260 ppm   8.0                                         IV   1-ethoxy-4-trichloromethylphthalazine                                                            260 ppm   7.0                                         V    1-chloro-4-trichloromethylphthalazine                                                            260 ppm            10.0                               VI   1-chloro-4-trichloromethylphthalazine                                                            260 ppm                  6.0                          VII  1-ethoxy-4-trichloromethylphthalazine                                                            260 ppm                  6.0                          __________________________________________________________________________

EXAMPLES VIII AND IX

Leaves of young bean plants were dipped in an aqueous solutioncontaining 260 ppm (or 33 parts per million) of1-ethoxy-4-trichloromethylphthalazine. Next, 5- to 7-day old larvae ofSouthern armyworm, [Prodenia eridania (Cramer)], are placed upon them assoon as the chemical is dry. Observations are made on the extent ofinhibition of feeding two or three days later. This response was ratedfrom 0 (no effect on feeding) to 10 (total inhibition of feeding). Theresults are given in Table II below.

EXAMPLE X

Leaves of young bean plants were dipped in an aqueous solutioncontaining 260 parts per million of1-ethoxy-4-trichloromethylphthalazine. Next,5- to 7-day old larvae ofMexican bean beetle, (Epilachna varivestis Mulsart), are placed uponthem as soon as the chemical is dry. Observations are made on the extentof inhibition of feeding two or three days later. This response wasrated from 0 (no effect on feeding) to 10 (total inhibition of feeding).The results are given in Table II below.

                                      Table II                                    __________________________________________________________________________    INSECTICIDAL ACTIVITY                                                                                 Control of Feeding                                                            Conc. of Chemical    Mexican Bean                     Example                                                                            Chemical           in Solution                                                                             Southern Armyworm                                                                        Beetle                           __________________________________________________________________________    VIII 1-ethoxy-4-trichloromethylphthalazine                                                            260 ppm   10.0                                        IX   1-ethoxy-4-trichloromethylphthalazine                                                            33 ppm    6.0                                         X    1-ethoxy-4-trichloromethylphthalazine                                                            260 ppm              3.0                              __________________________________________________________________________

What is claimed is:
 1. A compound of the formula ##STR2## where X iseither a halo group or a lower alkoxy group.
 2. The compound of claim 1which is 1-halo-4-trichloromethylphthalazine.
 3. The compound of claim 2which is 1-chloro-4-trichloromethylphthalazine.
 4. The compound of claim1 which is 1-lower alkoxy-4-trichloromethylphthalazine.
 5. The compoundof claim 4 which is 1-ethoxy-4-trichloromethylphthalazine.